Valery Krizhanovsky, PhD

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Investigator Bio:   

Dr. Valery Krizhanovsky is a Professor in the Department of Molecular Cell Biology and the Director of the EKARD Institute of Cancer Diagnosis Research at the Weizmann Institute of Science. His laboratory studies the role of senescent cells in cancer and aging, as well as age-related pathologies, including neurodegenerative diseases. Current research at the Krizhanovsky lab uncovers how senescence in the organism and in specific tissues is regulated, and what the dynamics of senescent cells is during normal aging, age-related disease, and neurodegeneration in models of Alzheimer’s and Parkinson’s disease (PD). 

Objectives/Background:

This project explores whether a distinct population of aged immune cells in the brain, known as senescent microglia, contributes directly to the development of PD. These cells accumulate with age and adopt a proinflammatory profile that might promote disease. Although brain inflammation is recognized as a hallmark of PD, the specific role of senescent microglia in sustaining this response remains unclear. By clarifying their contribution, this research aims to identify new mechanisms driving disease state and potentially new drug targets. 

Methods/Design:

We will combine well-studied mouse models that mimic PD with advanced genetic tools to investigate how removing only the microglia (brain immune cells) that have become old and no longer work properly will affect how PD develops. We will examine changes in movement alongside signs of inflammation in the brain, changes in brain cells, and which genes are turned on or off. We will look at brain tissue under a microscope, measure specific molecules, and study gene activity to enable us to define the exact role these aged brain immune cells play in causing brain inflammation and damage in PD. 

Relevance to Diagnosis/Treatment of Parkinson’s Disease:

This study will determine whether removing or controlling aged brain immune cells reduces brain inflammation and PD pathology. Demonstrating a direct role for these cells could inform new therapeutic strategies focused on aged immune cells. In parallel, the identification of unique patterns of molecules associated with senescent microglia has the potential to help create new tests to diagnose PD earlier and track how well treatments are working.